The purpose of this project is to improve understanding of the role of specific neurotransmitter systems in information processing in the basal ganglia with the goal of developing better strategies for pharmacological treatment of neurological disorders. The following topics are currently under investigation: (1) Processes involved in modulation substantia nigra (SN) dopamine cell activity. Dopamine neurons have been found to be either tonically active or quiescent under normal conditions. The role of SN pars reticulata GABAergic neurons and corticonigral glutamatergic inputs in regulation of tonic dopamine cell activity are being explored in studies which indicate that neither of these neuronal systems exert a prominent effect on tonic dopamine firing. This supports the potential significance of dopamine autoreceptor-mediated inhibitory processes modulating intrinsically generated spontaneous dopamine cell discharge. (2) Influence of SN dopamine neurons and striatal efferents on the cells of the SN pars reticulata and the external globus pallidus. Alterations in the inputs to the SN pars reticulata and the globus pallidus may underlie symptomotology of Parkinsonism,, tardive dyskinesia and Huntington's Chorea. Results have shown that dopamine can modulate the effects of GABA on pars reticulata and globus pallidus neurons. This modulatory interaction between dopamine and GABA can occur with physiological release of the two transmitters within the substantia nigra, supporting the idea that dopamine released from dopamine denddrites may directly influence SAN pars reticulata output neurons. While globus pallidus neurons respond like the SN pars reticulata cells to iontophoretically applied dopamine, they respond differently to i.v. administration of dopamine agonists in normal animals and in those in which dopamine neurons have been lesioned, providing an animal model of Parkinsonism. These results suggest these regions cannot be considered pharmacologically or functionally lanalogous output nuclei of the basal ganglia, and provide insight into the actions of dopamine agonists in Parkinsonism.